ArticleBlood2012
The mitochondrial ATP-dependent Lon protease: a novel target in lymphoma death mediated by the synthetic triterpenoid CDDO and its derivatives.
Article in Blood, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 89 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
89 citing papers in PubMed, 139 citations in OpenAlex.
- Lonp1 expression and correlation with mitophagy and immune infiltration markers in colon adenocarcinoma.Histology and histopathology · 2026Article
- Molecular mechanisms of mitochondrial AAA+ proteases.The Journal of biological chemistry · 2026Review
- LONP1 regulation of mitochondrial protein folding provides insight into beta cell failure in type 2 diabetes.Nature metabolism · 2025Article
- The mitochondrial LONP1 protease: molecular targets and role in pathophysiology.Molecular biology reports · 2025Review
- Modulation of Lonp1 Activity by Small Compounds.Biomolecules · 2025Review
- Mitochondrial complex-1 as a therapeutic target for cardiac diseases.Molecular and cellular biochemistry · 2025Review
- Machine learning-aided discovery of T790M-mutant EGFR inhibitor CDDO-Me effectively suppresses non-small cell lung cancer growth.Cell communication and signaling : CCS · 2024Article
- Review
- Redox regulation of UPR signalling and mitochondrial ER contact sites.Cellular and molecular life sciences : CMLS · 2024Review
- Polyphosphate and tyrosine phosphorylation in the N-terminal domain of the human mitochondrial Lon protease disrupts its functions.Scientific reports · 2024Article
- Intraneuronal β-amyloid impaired mitochondrial proteostasis through the impact on LONP1.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Temporal landscape of mitochondrial proteostasis governed by the UPRScience advances · 2023Article
- Protease-independent control of parthanatos by HtrA2/Omi.Cellular and molecular life sciences : CMLS · 2023Article
- Proteolytic rewiring of mitochondria by LONP1 directs cell identity switching of adipocytes.Nature cell biology · 2023Article
- mtUPR Modulation as a Therapeutic Target for Primary and Secondary Mitochondrial Diseases.International journal of molecular sciences · 2023Review
- Article
- Roles of LonP1 in Oral-Maxillofacial Developmental Defects and Tumors: A Novel Insight.International journal of molecular sciences · 2022Review
- Mitochondrial proteotoxicity: implications and ubiquitin-dependent quality control mechanisms.Cellular and molecular life sciences : CMLS · 2022Review
- Mitochondrial oxidative stress in the tumor microenvironment and cancer immunoescape: foe or friend?Journal of biomedical science · 2022Review
- Protein import motor complex reacts to mitochondrial misfolding by reducing protein import and activating mitophagy.Nature communications · 2022Article
29 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
Synthetic triterpenoids are multitarget compounds exhibiting promise as preventative and therapeutic agents for cancer. Their proposed mechanism of action is by forming Michael adducts with reactive nucleophilic groups on target proteins. Our previous work demonstrates that the 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO) and its derivatives promote B-lymphoid cell apoptosis through a mitochondria-mediated pathway linked to mitochondrial protein aggregation. As one function of the Lon protease is to eliminate abnormal mitochondrial proteins, we hypothesized that CDDO-induced protein aggregation and lymphoma apoptosis occur by inactivating this enzyme. Here, we show that CDDO and its derivatives directly and selectively inhibit Lon. CDDO blocks Lon-mediated proteolysis in biochemical and cellular assays, but does not inhibit the 20S proteasome. Furthermore, a biotinylated-CDDO conjugate modifies mitochondrial Lon. A striking common phenotype of CDDO-treated lymphoma cells and Lon-knockdown cells is the accumulation of electron-dense aggregates within mitochondria. We also show that Lon protein levels are substantially elevated in malignant lymphoma cells, compared with resting or activated B cells. Finally, we demonstrate that Lon knockdown leads to lymphoma cell death. Together, these findings suggest that Lon inhibition plays a contributory role in CDDO-induced lymphoma cell death, and support the concept that mitochondrial Lon is a novel anticancer drug target.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.